Landsteiner realized that “natural” antibodies develop that are directed against antigens not present on the red cells. Individuals with “A” antigens on their red cells had sera containing “Anti-B” antibody. Individuals with “B” antigens had sera containing “Anti-A," and “O” individuals’ sera contained “Anti-A” and “Anti-B.”

Subsequent researchers determined that “AB” individuals had sera with no ABO antibodies present and sera from group O individuals may also contain a separate antibody, “Anti-A,B.” Anti-A,B possesses serologic activity not found in mixtures of Anti-A and Anti-B. Anti-A,B sera will agglutinate A, B, and AB cells. (This is particularly useful in detecting weak A and B antigens). See the table on the next page.